Drug detection in oral fluid and urine after single therapeutic doses of dexamphetamine, lisdexamphetamine, and methylphenidate in healthy volunteers.

Abstract

Dexamphetamine, lisdexamphetamine, and methylphenidate are central stimulant drugs widely used to treat Attention-deficit/hyperactivity disorder (ADHD), but poor adherence may lead to treatment failure and the drugs are also subject to misuse and diversion. Drug analysis in oral fluid may thus be useful for monitoring adherence and misuse. We measured drug concentrations in oral fluid and urine after controlled dosing to investigate detection windows and evaluate the chosen cut-offs. Healthy volunteers ingested single oral doses of 10 mg dexamphetamine (n=11), 30 mg lisdexamphetamine (n=11), or 20 mg methylphenidate (n=10), after which they collected parallel oral fluid and urine samples every 8 hours for 4-6 days. Amphetamine (analytical cut-off, oral fluid: 1.5 ng/mL; urine: 50 ng/mL), methylphenidate (oral fluid: 0.06 ng/mL), and ritalinic acid (urine: 500 ng/mL) were analyzed using fully validated chromatographic methods. The median time from ingestion to the last detection in oral fluid was 67 ± 4.9 (lisdexamphetamine) and 69 ± 8.8 (dexamphetamine) hours for amphetamine and 36 ± 2.5 hours for methylphenidate. This was comparable to urine (77 ± 5.1 hours for lisdexamphetamine, 78 ± 4.5 hours for dexamphetamine, 41 ± 2.4 hours for ritalinic acid). The inter-individual variability in detection times was large, probably in part due to pH-dependent disposition. Using a logistic regression approach, we found similar detection rates as a function of time since intake in urine and oral fluid with the chosen cut-offs, with a high degree of probability for detection at least 24 hours after intake of a low therapeutic dose. This demonstrates the usefulness of oral fluid as a test matrix to assess adherence to ADHD medications, provided the analytical method is sensitive, requiring a cut-off as low as 0.1 ng/mL for methylphenidate. Detection windows similar to those in urine may be achieved for amphetamine and methylphenidate in oral fluid.